study of actr087 in subjects with relapsed or refractory b-cell lymphoma

Conditions: Lymphoma

Summary: this is a phase 1, multi-center, single-arm, open-label study evaluating the safety and efficacy of an autologous t-cell product expressing actr in combination with rituximab in subjects with refractory or relapsed cd20+ b-cell lymphoma.


Eligibility criteria:
inclusion criteria: * signed written informed consent obtained prior to study procedures * histologically-confirmed relapsed or refractory cd20+ b-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy: * dlbcl, regardless of cell of origin or underlying molecular genetics * mcl * pmbcl * gr3b-fl * th-fl * biopsy-confirmed cd20+ expression of the underlying malignancy by immunohistochemical staining or flow cytometry between the most recent dose of an anti-cd20 monoclonal antibody (mab) and study enrollment * at least 1 measurable lesion on imaging. lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy * must have received adequate prior therapy for the underlying cd20+ b-cell lymphoma, defined as an anti-cd20 mab in combination with an anthracycline-containing chemotherapy regimen (i.e. chemo-immunotherapy) and at least one of the following: * biopsy-proven refractory disease after frontline chemo-immunotherapy * relapse within 1 year from frontline chemo-immunotherapy and ineligible for autologous hematopoietic stem cell transplant (auto-hsct) * for subjects with dlbcl, pmbcl, and gr3b-fl: relapsed or refractory disease following at least 2 prior regimens or following an auto-hsct * for subjects with th-fl: relapsed or refractory disease following at least 2 prior regimens or following an auto-hsct. at least 1 prior regimen with an anti-cd20 mab in combination with chemotherapy is required following documented transformation * for subjects with mcl (confirmed with cyclin d1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (fish) or pcr): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-hsct is allowable) * karnofsky performance scale ≥ 60% * life expectancy of at least 6 months * anc \> 1000/µl * platelet count \> 50,000/µl * for women of childbearing potential (defined as physiologically capable of becoming pregnant), agreement to use of highly effective contraception for at least 1 year following actr087 infusion. for men with partners of childbearing potential, agreement to use effective barrier contraception for at least 1 year following actr087 infusion exclusion criteria: * known active central nervous system (cns) involvement by malignancy. subjects with prior cns involvement with their lymphoma must have completed effective treatment of their cns disease at least 3 months prior to enrollment with no evidence of disease clinically and at least stable findings on relevant cns imaging * prior treatment as follows: * alemtuzumab within 6 months of enrollment * fludarabine, cladribine, or clofarabine within 3 months of enrollment * external beam radiation within 2 weeks of enrollment * mab (including rituximab) within 2 weeks of enrollment * other lymphotoxic chemotherapy (including steroids except as below) within 2 weeks of enrollment * experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy * serum creatinine ≥ 1.5 x age-adjusted upper limits of normal (uln) * pulse oximetry \< 92% on room air * direct bilirubin ≥ 3.0 mg/dl (50 mmol/l) * alanine transaminase (alt) ≥ 3 times the uln, unless determined to be directly due to lymphoma. * aspartate transaminase (ast) ≥ 3 times the uln, unless determined to be directly due to lymphoma * class iii or iv heart failure as defined by the new york heart association (nyha), history of cardiac angioplasty or stenting, documented myocardial infarction or unstable angina within 6 months prior to enrollment, cardiac ejection fraction of \< 45%, or other clinically significant cardiac disease * clinical history of, prior diagnosis of, or overt evidence of autoimmune disease, regardless of severity * clinically significant active infection, in the judgment of the investigator * pregnancy (negative serum pregnancy test to be obtained within 6 days prior to enrollment for subjects of childbearing potential) * breastfeeding * primary immunodeficiency * seropositive for human immunodeficiency virus (hiv) 1 or hiv 2, or positive hepatitis b surface antigen (hbsag) or hepatitis c antibody * will need or has needed active treatment of a second malignancy within the prior 3 years before enrollment, other than fl, non-melanoma skin cancers, localized prostate cancer treated with curative intent, or cervical carcinoma in situ * is unable to receive any of the agents used in this study due a history of severe immediate hypersensitivity reaction (e.g. hypersensitivity to dimethyl sulfoxide (dmso)) * history of prior allogeneic hsct * history of richter's transformation from cll * prior infusion of a genetically modified therapy

Keywords: cd20+ b-cell actr087 relapsed refractory